4C:ARA20 | CD19‐BCMA Dual Targeted CAR‐T Therapy in Refractory Systemic Lupus Erythematosus

Aims: To prospectively define peripheral immune kinetics following tandem CD19/BCMA CAR-T therapy in refractory systemic lupus erythematosus (SLE) and identify pharmacodynamic signatures of on-target suppression and immune reconstitution. Methods: In this prospective investigator-initiated trial (IIT), seven patients with refractory SLE received autologous tandem CD19/BCMA CAR-T cells. Serial standardized multiparameter flow cytometry was performed to quantify B-lineage depth (CD19+ B-cells, CD138+ plasma cells), T-cell subsets (CD3+, CD4+, CD8+), and innate effectors (NK/NKT). Primary endpoints included depletion nadir (targeting undetectable levels) and longitudinal reconstitution trajectories. Results: Rapid, deep B-lineage suppression was observed post-infusion. Crucially, CD19+ B-cells and CD138+ plasma cells dropped to 0.00% (below detection limits) in 7/7 patients within the first month, signifying destruction of the autoantibody-producing reservoir. This deep aplasia was sustained throughout observation. Concurrently, the immune landscape underwent significant reprogramming: lymphocyte counts recovered driven by robust CD3+ T-cell expansion. CD4/CD8 ratios demonstrated dynamic inversion and subsequent normalization, reflecting homeostatic recovery. Innate subsets (NK/NKT) remained preserved, providing essential immunity during B-cell aplasia. This profile confirms a “hard reset” rather than transient suppression. Conclusion: Tandem CD19/BCMA CAR-T therapy induces a deeper immunologic reset than conventional therapies by effectively eliminating the plasma cell compartment. The observed kinetics—characterized by “zero-level” depletion and coordinated T-cell reconstitution—highlight the potential of this modality to halt autoimmunity at its source. These findings validate detailed immunoprofiling as a critical biomarker for verifying therapeutic depth in next-generation SLE management.